GRETeL: Tumor Response to Standard Radiotherapy and TMZ Patients With GBM

Sponsor

Duke University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05695976

Collaborator

Personalis, Inc. (Other)

100

Enrollment

Location

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to better define longitudinal genomic alterations in patients with glioblastoma (GBM), and to determine if plasma circulating tumor DNA (ctDNA) or cell free DNA (cfDNA) is associated with disease recurrence, survival, tumor characteristics, and/or peripheral immunosuppression.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Glioma, Malignant

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Study for Patients Newly Diagnosed With Glioblastoma Being Treated With Standard Radiotherapy and Temozolomide (TMZ) to Evaluate Tumor Response Via Liquid Biopsies (GRETeL)

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2029

Anticipated Study Completion Date :

Jan 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Pilot The first 20 patients accrued to this study will be assayed to validate the performance of the assays developed by Personalis. This pilot sub-study will be analyzed in a "blinded" manner without clinical information.
Full Study The remaining 80 patients accrued to this study (after the initial 20 patients accrue to the "Pilot" cohort).

Outcome Measures

Primary Outcome Measures

Median cf/ctDNA concentration at pre- and post-radiation, as well as median change in ct/ctDNA concentration [6 months]
Identify and describe changes in the cell free DNA (cfDNA) sequencing profiles of patients diagnosed with GBM in pre- versus post-radiation therapy samples, and to assess the association between these changes and clinical outcome, including progression free and overall survival
Median levels of cfDNA collected longitudinally after completion of radiation [6 months]
Identify and describe changes over time after radiotherapy in the cfDNA sequencing profiles of patients diagnosed with GBM, and to assess the association between these longitudinal changes in cfDNA and clinical outcome, including progression free and overall survival

Other Outcome Measures

Characterize the fragmentomic landscape of GBM [6 months]
Median number of ctDNA fragments obtained from tumor tissue, pre-radiation serum specimen, and post-radiation serum specimen, and healthy controls.
Spearman correlation between clinical descriptors and measures of ctDNA [6 months]
Assess the association between degree and frequency of ctDNA shedding and clinical characteristics, such as molecular findings, histopathological characteristics, corticosteroid use, and bevacizumab use.
Median and range for measures of tumor immune infiltration [6 months]
Quantify the level of immune infiltration in the tumor, and assess its association with progression-free survival (PFS), overall survival (OS), and ctDNA detection.
Hazard ratio for the relationship between chromosomal instability and OS or PFS [6 months]
Assess the prognostic value of chromosomal instability/CAN burden, and assess its association with ctDNA from plasma.
Spearman correlation between ctDNA and peripheral T cell function, autoantibodies. [6 months]
Determine if peripheral T cell function and stemness or autoantibodies are association with ctDNA levels, or TME composition.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years
Patients newly diagnosed with malignant glioma, IDH wildtype who have undergone surgical resection for their tumor and who are planned for standard of care radiation therapy with concurrent temozolomide (i.e., at least 59 Gy in 30 fractions over 6 weeks)
Patients must have leftover tissue available from the surgical resection of their tumor available to request for this research.
Able to undergo MRI of brain with and without contrast
Signed informed consent approved by the Institutional Review Board (IRB)

Exclusion Criteria:

Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin